This project has clinical and basic components. We continue in our endeavors to understand the determinants of prognosis in the pediatric non-Hodgkins lymphomas and to develop improved combination chemotherapy. The results of our present treatment protocol for small non-cleaved cell (SNCL) and large cell lymphomas appear to be excellent (approximately 90% of patients are cured), so that at this time our clinical therapeutic studies are directed towards a) attempting to ameliorate toxicity with this combination regimen; and b) documenting the late effects of chemotherapy encountered by patients treated on all of our lymphoma protocols. Our basic studies are directed towards the elucidation of the molecular biology and molecular epidemiology of the SNCL. Major areas of investigation include a) detailed characterization of the non-random chromosomal translocations particularly 8;14 translocations associated with the SNCL with a view to understanding the immediate causes of enoplastic behavior and the determinants of geographic and clinical heterogeneity; b) the elucidation of the nature of the association of Epstein-Barr virus (EBV) with the SNCL; c) the examination of selected biological and clinical aspects of lymphomas associated with HIV infection; d) the elucidation of the pathogenetic significance of the mutations in the coding region of the c-myc gene recently discovered in this laboratory; e) the exploration of other molecular abnormalities of potential interest (both to pathogenesis and therapeutic outcome in the SNCL, in particular mutations in p53. Stemming from these studies, we are also investigating the possibility that the molecular abnormalities can be used as a target for tumor-specific treatment approaches.